title: Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs.
abstract: The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)-administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra-high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter-dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 μg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (μg/mL) can be predicted taking into account the OTC concentrations in plasma (μg/mL), according to the following equation: OTC(nasal secretions)  = 0.28 OTC(plasma) -1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single-dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non-compartmental analysis. In plasma, the maximum concentration of drug (C(max) ), the time at which this maximum concentration of drug (T(max) ) was reached, the elimination half-life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 μg/mL, 4.0, 5.1 h and 150 μg·h/mL. In nasal secretions, C(max) , T(max) , t½ and AUC were, respectively, 6.29 μg/mL, 4.0, 6.6 h and 51.1 μg·h/mL.
authors.affiliation: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Bimazubute
authors.forename: C
authors.initials: C
authors.lastname: Cambier
authors.forename: K
authors.initials: K
authors.lastname: Baert
authors.forename: S
authors.initials: S
authors.lastname: Vanbelle
authors.forename: P
authors.initials: P
authors.lastname: Chiap
authors.forename: P
authors.initials: P
authors.lastname: Gustin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D008297:Male; D009296:Nasal Cavity / Q000737:chemistry*; D010118:Oxytetracycline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013552:Swine / Q000097:blood / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D010118:Oxytetracycline